The transduction mechanism of the pain receptor in the corneal epithelium will be examined by electrophysiological, pharamacological and psychophysical techniques. Interaction between various stimulation modalities, e.g., touch, osmotic pressure and temperature, will be tested for summation and cross adaptation to examine whether they share pathways. The intervention of a chemical transmitter, liberated from the epithelial cells, will be looked for by testing the influence of active agents and their inhibitors on the threshold of reception. The perfusate of the isolated cornea will be examined for direct evidence of release of transmitter on stimulation of the entire corneal surface. Transmitters to be studied include acetylcholine, potassium and kinins. It will be necessary to know the concentration of the agents at the receptor terminals, and a subsidiary project will be to determine the dynamics of solute transfer through the paracellular spaces of the epithelium and how this would be affected by cellular uptake or enzymatic breakdown of the solute. Prolonged use of local anesthetics leads to corneal ulceration, and the mechanism will be studied by the continuous perfusion of low levels of anesthetic over the corneal surface or locally into the stroma. Changes in function and structure of the corneal eptielium similar to those following denervation will be looked for. Evidence of axonal transport in the trigeminal nerve will be sought, and if it is found attempts will be made to block it and the effect on the cornea noted. An attempt will be made to test if local anesthesia results in an interruption of axonal transport.